Tricho-dento-osseous syndrome(TDO) is an autosomal dominant disorder affecting hair, teeth and bone. The presence of defects in both ectodermal and mesenchymal tissues in TDO suggests that essential and shared processes of tissue formation exist and are dysfunctional. These investigations are undertaken to establish the molecular basis of TDO which is essential to understanding the pathogenesis of this disorder. Immediate goals are the characterization of the TDO phyotype and phenotypic variability in two large populations with TDO, and to establish a genomic locus linked to the TDO trait. In addition to the importance of this information to diagnosis and treatment of individuals with TDO, these studies are expected to provide basic information on the metabolic nature and molecular basis of excess bone formation that is characteristic of TDO and could be of great therapeutic significance for individuals with osteoporosis. The proposal for this study has just received NIH-NIDR funding. [unreadable]